Endogenous activated protein C is essential for immune-mediated cancer cell elimination from the circulation

G. L. van Sluis; L. W. Brüggemann; C. T. Esmon; P. W. Kamphuisen; D. J. Richel; H. R. Büller; C. J. F. van Noorden; C. A. Spek

doi:https://doi.org/10.1016/j.canlet.2011.02.038

Endogenous activated protein C is essential for immune-mediated cancer cell elimination from the circulation

G. L. van Sluis, L. W. Brüggemann, C. T. Esmon, P. W. Kamphuisen, D. J. Richel, H. R. Büller, C. J. F. van Noorden, C. A. Spek

Research output: Contribution to journal › Article › Academic › peer-review

15 Citations (Scopus)

Abstract

Fibrinogen and platelets play an important role in cancer cell survival in the circulation by protecting cancer cells from the immune system. Moreover, endogenous activated protein C (APC) limits cancer cell extravasation due to sphingosine-1-phosphate receptor-1 (S1P1) and VE-cadherin-dependent vascular barrier enhancement. We aimed to study the relative contribution of these two mechanisms in secondary tumor formation in vivo. We show that fibrinogen depletion limits pulmonary tumor foci formation in an experimental metastasis model in C57B1/6 mice but not in NOD-SCID mice lacking a functional immune system. Moreover, we show that in the absence of endogenous APC, fibrinogen depletion does not prevent cancer cell dissemination and secondary tumor formation in immune-competent mice. Overall, we thus show that endogenous APC is essential for immune-mediated cancer cell elimination. (C) 2011 Elsevier Ireland Ltd. All rights reserved

Original language	English
Pages (from-to)	106-110
Journal	Cancer Letters
Volume	306
Issue number	1
DOIs	https://doi.org/10.1016/j.canlet.2011.02.038
Publication status	Published - 2011

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https://doi.org/10.1016/j.canlet.2011.02.038

Cite this

@article{a60c34bde0574ec88e385089e12b8eb1,

title = "Endogenous activated protein C is essential for immune-mediated cancer cell elimination from the circulation",

abstract = "Fibrinogen and platelets play an important role in cancer cell survival in the circulation by protecting cancer cells from the immune system. Moreover, endogenous activated protein C (APC) limits cancer cell extravasation due to sphingosine-1-phosphate receptor-1 (S1P1) and VE-cadherin-dependent vascular barrier enhancement. We aimed to study the relative contribution of these two mechanisms in secondary tumor formation in vivo. We show that fibrinogen depletion limits pulmonary tumor foci formation in an experimental metastasis model in C57B1/6 mice but not in NOD-SCID mice lacking a functional immune system. Moreover, we show that in the absence of endogenous APC, fibrinogen depletion does not prevent cancer cell dissemination and secondary tumor formation in immune-competent mice. Overall, we thus show that endogenous APC is essential for immune-mediated cancer cell elimination. (C) 2011 Elsevier Ireland Ltd. All rights reserved",

author = "{van Sluis}, {G. L.} and Br{\"u}ggemann, {L. W.} and Esmon, {C. T.} and Kamphuisen, {P. W.} and Richel, {D. J.} and B{\"u}ller, {H. R.} and {van Noorden}, {C. J. F.} and Spek, {C. A.}",

year = "2011",

doi = "https://doi.org/10.1016/j.canlet.2011.02.038",

language = "English",

volume = "306",

pages = "106--110",

journal = "Cancer Letters",

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T1 - Endogenous activated protein C is essential for immune-mediated cancer cell elimination from the circulation

AU - van Sluis, G. L.

AU - Brüggemann, L. W.

AU - Esmon, C. T.

AU - Kamphuisen, P. W.

AU - Richel, D. J.

AU - Büller, H. R.

AU - van Noorden, C. J. F.

AU - Spek, C. A.

PY - 2011

Y1 - 2011

N2 - Fibrinogen and platelets play an important role in cancer cell survival in the circulation by protecting cancer cells from the immune system. Moreover, endogenous activated protein C (APC) limits cancer cell extravasation due to sphingosine-1-phosphate receptor-1 (S1P1) and VE-cadherin-dependent vascular barrier enhancement. We aimed to study the relative contribution of these two mechanisms in secondary tumor formation in vivo. We show that fibrinogen depletion limits pulmonary tumor foci formation in an experimental metastasis model in C57B1/6 mice but not in NOD-SCID mice lacking a functional immune system. Moreover, we show that in the absence of endogenous APC, fibrinogen depletion does not prevent cancer cell dissemination and secondary tumor formation in immune-competent mice. Overall, we thus show that endogenous APC is essential for immune-mediated cancer cell elimination. (C) 2011 Elsevier Ireland Ltd. All rights reserved

AB - Fibrinogen and platelets play an important role in cancer cell survival in the circulation by protecting cancer cells from the immune system. Moreover, endogenous activated protein C (APC) limits cancer cell extravasation due to sphingosine-1-phosphate receptor-1 (S1P1) and VE-cadherin-dependent vascular barrier enhancement. We aimed to study the relative contribution of these two mechanisms in secondary tumor formation in vivo. We show that fibrinogen depletion limits pulmonary tumor foci formation in an experimental metastasis model in C57B1/6 mice but not in NOD-SCID mice lacking a functional immune system. Moreover, we show that in the absence of endogenous APC, fibrinogen depletion does not prevent cancer cell dissemination and secondary tumor formation in immune-competent mice. Overall, we thus show that endogenous APC is essential for immune-mediated cancer cell elimination. (C) 2011 Elsevier Ireland Ltd. All rights reserved

U2 - https://doi.org/10.1016/j.canlet.2011.02.038

DO - https://doi.org/10.1016/j.canlet.2011.02.038

M3 - Article

C2 - 21420234

SN - 0304-3835

VL - 306

SP - 106

EP - 110

JO - Cancer Letters

JF - Cancer Letters

IS - 1

ER -